Are microbial limit tests required for sterile products?

[v9991]

in a sterile preparation, my query is on criteria for assessing the need of excluding
1) "Microbial Limit test" (MLT) (in-addition-to test for sterility )
2) BET test(BET) ,( considering that input materials are controlled, and process is qualified (media fill, area qualification etc),

can we invoke, Microbial Contamination Risk Level of Compounded sterile preparations (CSPs) of USP <797> PHARMACEUTICAL COMPOUNDING?STERILE PREPARATIONS for excluding MLT & BET

In-fact for some of the USP monographs of "sterile water for injection", do not contain tests for microbial limit tests.
BUT, there is indirect reference for inclusion of Microbial limit test, but not specific and exact references.

* * * *

https://www.gpo.gov/fdsys/pkg/CFR-2011-title21-vol4/pdf/CFR-2011-title21-vol4-sec200-51.pdf
? 200.51 Aqueous-based drug products for oral inhalation.
(a) All aqueous-based drug products for oral inhalation must be manufactured to be sterile.
(b) Manufacturers must also comply with the requirements in ? 211.113(b) of this chapter.
[65 FR 34089, May 26, 2000]

* * * *
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=211.113

Sec. 211.113 Control of microbiological contamination.
(a) Appropriate written procedures, designed to prevent objectionable microorganisms in drug products not required to be sterile, shall be established and followed.

(b) Appropriate written procedures, designed to prevent microbiological contamination of drug products purporting to be sterile, shall be established and followed. Such procedures shall include validation of all aseptic and sterilization processes.

[43 FR 45077, Sept. 29, 1978, as amended at 73 FR 51932, Sept. 8, 2008]

* * * *

 

[Ajit Basrur]

Re: Are microbial load tests required for sterile products?

There are 2 aspects to your question - the first being a test adopted in routine batch release and the other, being part of the validation studies.

When it comes to Batch Release, the sterility is an absolute term which means the articles are either sterile or non sterile and the Sterility Test gives that verdict. In these cases, the Microbial Limits Test is not a requirement.

However, as part of the sterilization process, it has to be validated and thus the Microbial Limits Tests can be part of that design and validation. The pre- and post-sterilization studies are undertaken to assure the effectiveness of a validated sterilization process.

 

[v9991]

Re: Are microbial load tests required for sterile products?

Thank you...

When it comes to Batch Release, the sterility is an absolute term which means the articles are either sterile or non sterile and the Sterility Test gives that verdict. In these cases, the Microbial Limits Test is not a requirement.

can we same/similar rationale for BET test? pl guide.

 

[Ajit Basrur]

Re: Are microbial load tests required for sterile products?

Thank you...


can we same/similar rationale for BET test? pl guide.

No, you can not ... the sterility test looks for live organisms while the BET levels indicate for debris of live and dead bacteria.

You have to perform BET even for sterile products.